| Fcα/μR is the Fc receptor for Immunoglobulin A(IgA) and Immunoglobulin M(IgM). It is a single gene-family member encoded on Chromosome 1q32 near several other FcR genes.The mouse Fcα/μR is a high affinity receptor for IgM,intermediate affinity receptor with monolgA.The human Fcα/μR represents a typeⅠtransmembrane protein of 522 amino acids,3 extracellular domains containing one Ig-like domain(EC2).This EC2 domain contains a conserved motif present in the first EC loop of human,bovine, and murine pIgR,suggesting an ancestral link and function.The mouse Fcα/μR is expressed on thymus,spleen,liver,kidney,small and large intestines,testis,and on hematopoietic cells,such as mature B cell and macrophages. Human Fcα/μR expressed in kidney,small intestine,and secondary lymphoid organs. In order to determine Fcα/μR precise role regarding the immune defense system,and distinguish its expression from plgR,we made monoclonal antibodies to Fcα/μR and pIgR.The cDNAs of the extracellular region of human Fcα/μR and plgR were inserted into pET30a plasmid and expressed as inclusion bodies in Escherichia coli. The purified proteins were used to immunize Balb/c mice and to generate hybridomas. The monoclonal antibodies were characterized by ELISA,flow cytometry,Western blotting and immunochemical analysis.Tissue distribution analysis was done using human multiple tissue arrays.Immunohistochemical analysis of human multiple tissues showed that the epithelial cells of renal tubules and human mesangium in glomeruli,some germinal center of spleen,lymphoid node and appendix,and some plasma cells in lamina propria of digestive tracts all express Fcα/μR.The epithelial cells of small and large intestines or pulmonary alveolus and gall bladder were strongly stained by anti-pIgR mAbs.Other tissues,such as the fundic glands of stomach,mammary gland,testis,prostate and cardiac muscle had different degree of positive staining by both receptors.Brain was positive for Fcα/μR stain.In brief,human Fcα/μR is wildly expressed on many tissues of human body.Compared to pIgR,Fcα/μR focus on these two kinds of tissue,the majority of lymphoid tissue located within the lining of the major tracts including respiratory,digestive and genitourinary tracts;and some epithelial cells of co-expressed with plgR,such as mammary gland and kidney.And the two tgA receptor can perform different function at the different lateral side of epithelial cells,transcytosis or receptor-mediating phagocytes. IgA nephropathy(IgAN) is the most common form of glomerulonephritis and is one of the principal causes of renal failure worldwide.The pathogenic mechanisms underlying IgAN are poorly understood.Using monoclonal antibodies specifically to Fcα/μR,we detected that the receptor could be expressed on primarily cultured human mesangial cells(HMC),human proximal tubular epithelial cells(PTEC) and HK-2 cells(a normal human proximal tubular cell line).The Fcα/μR expressed on HK-2 cells is a functional IgA receptor.The neutralizing antibody against Fcα/μR can block the binding of pIgA2 and serum IgA to HK-2 cells,and the phagocytosis for IgA/IgM immune complex.Immunohistochemistry analysis on biopsy subjects showed that Fcα/μR expression was increased in both glomeruli and renal tubules from IgAN.Dual-labeling studies demonstrated that IgA deposits in IgAN patients were co-localized with Fcα/μR in the glomeruli and renal tubules.Compared to controls,avidity between IgA and Fcα/μR was increased in IgAN patients.The binding could be inhibited up to 80%by anti-Fcα/μR monoclonal antibodies.Sera or purified IgA from IgAN patients could significantly up-regulate Fcα/μR expression on HK-2 cells and PTEC.These data indicated that Fcα/μR might be involved in pathogenesis of IgAN.
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